Case report of neurotoxicity with blinatumomab and concurrent intrathecal chemotherapy in second relapse of acute lymphoblastic leukemia with central nervous system disease

Abstract

A 26-year-old male with a history of pre-B cell acute lymphoblastic leukemia and seizures presented with second relapse of acute lymphoblastic leukemia and central nervous system involvement, 19 years after the initial diagnosis. Over the next two months, the patient received six doses of triple intrathecal chemotherapy (cytarabine, methotrexate, and hydrocortisone), three concurrently with continuous blinatumomab in the second month. Approximately 12 days after blinatumomab initiation, he developed central nervous system toxicity manifesting as speech impairment, altered mental status, incontinence, and diffuse weakness. Blinatumomab was discontinued, and he was started on dexamethasone. Within the next couple of months, his neurologic status recovered, and he was able to perform all of his baseline activities without limitation. Unfortunately, the patient eventually expired after further relapse approximately one year later. To our knowledge, this is the first published case report of severe neurotoxicity in a patient who was given blinatumomab concurrently with intrathecal chemotherapy.

The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials

“…The condition resolved despite the resumption of treatment 84 Neurotoxicity with blinatumomab and concomitant intrathecal chemotherapy 85 Neurotoxicity 9 days after completion of cycle 1 blinatumomab infusion with intrathecal methotrexate injections at D15 and D29.…”

“… 84 Neurotoxicity with blinatumomab and concomitant intrathecal chemotherapy. 85 Neurotoxicity 9 days after completion of cycle 1 blinatumomab infusion with intrathecal methotrexate injections at D15 and D29. Toxicity was non‐reversible despite numerous treatments (corticosteroids, anticonvulsants, etc.).…”

Blinatumomab use in pediatric ALL: Taking a BiTE out of preparation, administration and toxicity challenges

“…Some case reports suggested increased neurotoxicity with concurrent IT and blinatumomab administration. 33 IT therapy during blinatumomab blocks was administered in both COG AALL1331 trial and the currently enrolling COG AALL1731 frontline trial. There was no increase in neurological adverse events noticed in AALL1331 trial during blinatumomab blocks.…”

Blinatumomab-related pneumatosis intestinalis in a pediatric patient with relapsed acute lymphoblastic leukemia: A case report

“…1,2 Despite its promising efficacy, adverse effects include significant cytokine release syndrome, neurotoxicity, febrile neutropenia, and rarely pneumatosis intestinalis (PI). [3][4][5] PI may be a benign finding that is incidentally identified as the presence of air in the subserosal or submucosal layer of the intestine, but can be a sign of serious conditions, such as bowel ischemia and perforation, and may require surgery. 6,7 To date, only a few patients have developed PI after receiving molecular targeted therapy, but these reports involved bevacizumab, sunitinib, and gefitinib therapy in adult patients.…”